Cytoplasmic flows guide chromosome positioning during embryogenesis

During the first stages of animal embryo development, the egg cell undergoes multiple divisions without growing, resulting in smaller and smaller cells. As cells become smaller, how do chromosomes, which bear the genetic material, know where to go and end up in the right position to make the nuclei? This is particularly intriguing because, in most cells, chromosomes are usually anchored to microtubules that are themselves anchored to the cell walls, pulling chromosomes during division. However, during embryogenesis, the microtubules do not touch the cell walls because the cells are too large. Additionally, the chromosomes are not tightly anchored to the microtubules. So, how do chromosomes move to the correct place without a control system? Dr. Olga Afonso and Prof. Marcos Gonzalez-Gaitan from the School of Chemistry and Biochemistry, Faculty of Science, University of Geneva, investigated this mystery. In their new study published in Nature Cell Biology, they discovered that currents, known as cytoplasmic flows, are generated in the cytoplasm during division. These flows act as a cell size sensor, ensuring that nuclear envelope reformation (NER) occurs at the correct position as cells divide and shrink.

During the rapid mitotic cycles of early embryogenesis, cells must maintain proportionality between their size and internal structures. The mechanism in most cells in the animal involves pulling of the chromosome, but this cannot be effective in the large cells of the animal embryo. In a new article, published in Nature Cell Biology, Prof. Gonzalez-Gaitan of the School of Chemistry and Biochemistry at the Faculty of Sciences, UNIGE and his team studied the mobility of chromosomes in embryos of the Zebrafish. The study found that nuclear envelope reformation (NER) adapts to cell size through changes in chromosome motility, mediated by cytoplasmic flows. Simply speaking, the researchers unveil the existence of flows in the cytoplasm of the cell during the division. The chromosomes, floating in the cytoplasm, are thus carried by the flow to the proper place in the cell before the new envelope is produced. 

Our findings reveal a fascinating mechanism by which cells sense their size and adjust their internal structures accordingly. This scaling mechanism is crucial for the proper development of the embryo and may have implications for understanding how cells maintain proportionality in other contexts as well.

-- Dr. Olga Afonso, the lead author of the study.

Microtubules do not touch the cell walls, making inefficient the classical mecanism which operates in other cell types where cell division has been studied so far. In early embryonic cells,the viscosity of the cytoplasm implies that the velocity of the flows in the fluid stay zero on the cell walls. The cancellation of the velocity at the edge automatically shape and scale the cytoplasmic flows and thus allow, to some extent, the cells to sense their size. As cells become smaller, the flows scale accordingly, ensuring that NER occurs at the correct position.

How do cytoplasmic flows appear?

At this scale, the cytoplasm appears to be an extremely viscous liquid, making it challenging for organelles to move, similar to a person trying to walk through quicksand. Microtubules, which are long filaments present in cells, serve as tracks for the transport of bulky cargo. This cargo is moved along microtubules by dynein, a motor protein that walks on the microtubules. The flows observed are actually generated by the friction between the viscous cytoplasm and the bulky cargo transported by dynein on microtubules.

The study utilized advanced imaging techniques and theoretical modeling, in collaboration with the group of Prof. Karsten Kruse, also from the School of Chemistry and Biochemistry, to demonstrate that cytoplasmic flows are independent of chromosome movement and function as a sensor for cell geometry. The researchers also showed that microtubules are essential for generating these flows, and that the flows scale with cell size due to the physical confinement of the cell.

This work not only advances our understanding of early embryogenesis, but also highlights the importance of physical mechanisms in cellular processes. We hope that our findings will inspire further research into the role of cytoplasmic flows in other cellular contexts and developmental processes.

-- Prof. Marcos Gonzalez-Gaitan, senior author of the study.